Table I.

Summary of the main inclusion and exclusion criteria and relapse definitions of RCTs and cohorts included in this comparative study.

Study	Study aim/description	Main eligibility criteria*	Main exclusion/restrictive criteria	Relapse definition/details/comments¶
Trials
WEG91 (2)	Oral vs. IV cyclophosphamide for induction of remission	age >15 years systemic GPA diagnosed clinically with multiorgan involvement (ENT and/or lung and/or rapidly progressive glomerulonephritis associated with severe general symptoms) monovisceral involvement representing a potential risk of severe morbidity or fatality positive histopathology	age <15 years	relapse = new major systemic manifestations of GPA affecting the same or a different organ than that initially involved, or worsening of the initial symptoms of the disease occurrence of arthralgias, sinusitis, rhinitis, or other minor clinical symptoms was not considered to represent a major relapse requiring withdrawal from the study 74% had renal involvement at diagnosis
WEGENT (3)	Azathioprine vs. methotrexate for remission maintenance, after IV cyclophosphamide for induction	newly diagnosed systemic GPA (renal disease, involvement of at least two organs or systems, or involvement of one organ or system and constitutional symptoms) or MPA with FFS ≥1†	age <18 years	relapse = recurrence or first appearance of one or more BVAS items attributable to active vasculitis in a patient previously in remission for >3 months all those recorded and reported relapses led to a change of immunosuppressant 75% had renal involvement at diagnosis
CYCLOPS (4)	Oral vs. IV cyclophosphamide for induction of remission	newly diagnosed GPA, MPA or renal- limited MPA, all with mild/moderate renal involvement¶	age <18 or >80 years creatinine level >500 μmol/L	major relapse = recurrence or first appearance of at least 1 BVAS item indicating threatened vital organ function attributable to active vasculitis minor relapse = recurrence or first appearance of ≥3 other BVAS items related to nonvital organs
CYCAZAREM (5)	Continued oral cyclophosphamide vs. early switch to azathioprine for remission maintenance	newly diagnosed GPA or MPA or renal-limited vasculitis with mild or moderate or other vital-organ involvement renal	age <18 or >75 years serum creatinine >500 μmol/L	major relapse = recurrence or first appearance of ≥1 of the 24 items on the BVAS indicative of threatened function of a vital organ attributable to active vasculitis minor relapse = recurrence or first appearance of ≥3 other items in the BVAS 94% had renal involvement at diagnosis
IMPROVE (6)	Azathioprine vs. mycophenolate mofetil for maintenance, after IV or oral cyclophosphamide for induction	new diagnosis of GPA or MPA age 18 to 75 years at diagnosis positive indirect immunofluorescence or ELISA test result for ANCAs	patients in whom the induction protocol failed to control progressive disease (1 patient) or achieve remission by 6 months (6 patients) were withdrawn**	major relapse = new appearance of major organ involvement attributable to active vasculitis minor relapse = recurrence or new occurrence of less severe disease attributable to active vasculitis*
Cohorts
FVSG	French multicentric observational cohort	all patients newly diagnosed with or followed for GPA or MPA and satisfying ACR criteria and/or Chapel hill definitions		patients can be enrolled at any time during the course of their disease, including at the early time of diagnosis; data from patients with early and rapid fatal outcomes can also be entered no scheduled follow-up visits (minimum one update every 2 years for each patient and in case of relapse or death)
VCRC-GPA-MPA	North American multicentric longitudinal protocol	all patients newly diagnosed with or followed for GPA, satisfying modified ACR criteria (nasal or oral inflammation; abnormal chest radiograph; urinary sediment abnormalities; granulomatous inflammation on biopsy; ANCA positivity by enzyme immunoassay for PR3 or myeloperoxidase-ANCA) or MPA, satisfying Chapel Hill definition		patients can be enrolled at any time during the course of their disease; however, most are enrolled during a follow-up visit rather than at the early time of diagnosis systematic and scheduled follow-up visits every 3 or 12 months (patient’s preference) or at the time of an event (relapse or death)

^*Patients with renal limited vasculitis and no general or constitutional symptoms were not included in this comparative study.

^¶Although definitions of minor relapses are reported in this table, those (minor) relapses that did not lead to a change in immunosuppressant therapy and/or patient RCT withdrawal were not included this comparative study.

^†The FFS prognostic score includes 5 parameters, each of them scoring for 1 point if present: elevated serum creatinine levels (140 moles/liter or 1.58 mg/dl), proteinuria (1 gm/day), severe gastrointestinal tract involvement, cardiomyopathy, and/or central nervous system (CNS) involvement.

^**Data form these 7 patients were not available in the RCT report or for this study.

ACR: American College of Rheumatology; ANCA: antineutrophil cytoplasm antibody; BVAS: Birmingham Vasculitis Activity Score; FVSG: French Vasculitis Study Group; FFS: five-factor score; GPA: granulomatosis with polyangiitis; IV: intravenous; MPA: microscopic polyangiitis; RCT: randomised controlled trial; VCRC: Vasculitis Clinical Research Consortium.